Abstract
Cells coexist together in colonies or as tissues. Their behavior is controlled by an interplay between intercellular forces and biochemical regulation. We develop a simple model of the cell cycle, the fundamental regulatory network controlling growth and division, and couple this to the physical forces arising within the cell collective. We analyze this model using both particle-based computer simulations and a continuum theory. We focus on 2D colonies confined in a channel. These develop moving growth fronts of dividing cells with quiescent cells in the interior. The profile and speed of these fronts are nontrivially related to the substrate friction and the cell-cycle parameters, providing a possible approach to measure such parameters in experiments.
- Received 14 December 2020
- Revised 15 April 2021
- Accepted 9 June 2021
DOI:https://doi.org/10.1103/PhysRevX.11.031025
Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.
Published by the American Physical Society
Physics Subject Headings (PhySH)
Popular Summary
Physicists and biologists often look at cell growth and division completely differently. A typical cell biologist understands the process in terms of the cell cycle, an internal biochemical regulator that selects proliferation or quiescence based on local cues. The role of physics might be seen as merely providing inputs to this central biochemical regulator. A typical physicist approaches the problem in almost opposite terms: The behavior of the tissue is essentially a physics problem to be treated, for example, using theories of active hydrodynamics. Here, we attempt a proper reconcilement of these viewpoints.
We address the cell cycle’s role in colony and tissue growth using particle-based simulations and analytic theory, focusing on 2D colonies confined in a channel. We develop a mechanochemical model, incorporating the cell cycle as a biochemical oscillator, sensitive to pressure, that controls cell division and size. Our goal is to present a relatively simple model that highlights the nontrivial role of the cell cycle. To do this in isolation, we deliberately make some simplifying assumptions, including neglecting active cell motility.
The variables that control the cell cycle are reference values for pressure, quiescent volume and growth rate, and two characteristic times for changes to volume and cell cycle activity. These all affect the emergent dynamics of growing colonies, such as the structure and speed of growing fronts. We also provide useful new results on the relationship between substrate friction and the growth front speed.
We hope this work motivates experiments to isolate and further evaluate the role of the cell cycle in collective cell dynamics.
